Detection of genetic polymorphisms of caspases-9, stromal cell-derived factor-1 and E-selectin in breast cancer

Caspases (CASPs), play a crucial role in the development and progression of cancer. We evaluated the association between two polymorphisms (rs4645978 and rs4645981) of the CASP9 gene and the risk of breast cancer (BC). Genotypes and allelic frequencies for the two polymorphisms were determined in 261 patients with breast cancer and 480 healthy controls. Polymerase chain reaction-restriction fragment length polymorphisms were used, and statistical significance was determined by the χ2 test. Carriers of the rs4645978 G allele (AG and GG genotypes) were at higher risk for BC than individuals with other genotypes (odds ratio (OR) 1.59, 95% confidence interval (CI) 1.07-2.37, p =0.022). The rs4645978 GG genotype, in particular, was associated with the highest risk for BC development (OR 2.25, 95% CI 1.45-3.49, p=0.0003). Similarly, individuals with at least one rs4645981 T allele were at a significantly increased risk of developing BC compared with those harboring the CC genotype (OR 2.75, 95% CI 1.99-3.78, p<0.0001), and the risk of BC increased with increasing numbers of rs4645981 T alleles (OR 2.66, 95% CI 1.91-3.69, p<0.0001 for the CT genotype; OR 3.95, 95% CI 1.58-9.88, p=0.004 for the TT genotype). The CASP9 promoter polymorphisms rs4645978 and rs4645981 are associated with BC susceptibility and suggest that CASP9 transcriptional regulation is an important factor during BC development. Breast cancer is prone to metastasis even in early stage disease. Stromal cell-derived factor-1 (SDF-1) is a chemokine that has been associated with the egress of cancer cells from the primary focus and homing to distant sites, while E-selectin has been implicated in their transendothelial migration. This study was performed to evaluate the association between SDF-1–3’ A and E-selectin S128R—two polymorphisms associated with enhanced function—and the risk of breast cancer, as well as their influence on breast cancer outcome. The frequencies for the wild-type (GG), GA and AA genotypes of SDF-1 were 43.7, 45.2, and 11.1 % in patients, and 51.5, 41.3, and 7.3 % in healthy controls, respectively, while the SDF-1–3’ A allelic frequency was 33.7 % at patients and 27.9 % at controls. The SDF-1–3’ A carrier group of patients and the A allele of SDF-1 were overrepresented among the breast cancer cases (p = 0.04 and 0.02, respectively). For the E-selectin S128R polymorphism, the frequencies for the wild-type (AA), AC and CC genotypes were 58.6, 38.3, and 3.1 % in patients and 63.8, 31.4, and 3.8 % in controls, respectively, while the C allelic frequency was 22.2 % for patients and 19.5 % for controls. The CC genotype was associated with poorer survival. Otherwise, no significant association was detected between examined genotypes and tumor characteristics. Overall, our findings support that the SDF-1–3’ A confers increased susceptibility to breast cancer and that the E-selectin S128R CC genotype may be related to poorer prognosis. Investigation in bigger cohorts of patients is warranted.Οι κασπάσες παίζουν έναν κρίσιμο ρόλο στην ανάπτυξη και την εξέλιξη του καρκίνου. Εκτιμήσαμε τη συσχέτιση ανάμεσα στους δύο πολυμορφισμούς (rs4645978 και rs4645981) του γονιδίου της κασπάσης-9 και τον κίνδυνο για καρκίνο του μαστού. Οι συχνότητες των γονοτύπων και των αλληλόμορφων για τους δύο πολυμορφισμούς καθορίστηκαν στους 261 ασθενείς και στους 480 υγιείς μάρτυρες. Χρησιμοποιήθηκε η αλυσιδωτή αντίδραση πολυμεράσης-πολυμερισμός μήκους θραυσμάτων από περιορισμό και η στατιστική ανάλυση έγινε με τη δοκιμασία χ2. Οι φορείς του rs4645978 G αλληλόμορφου (δηλαδή οι γονότυποι AG και GG) ήταν σε υψηλότερο κίνδυνο για καρκίνο του μαστού από τα άτομα με άλλους γονοτύπους. OR=1.59, 95% CI=1.07-2.37, p=0.022. O γονότυπος rs4645978 GG συγκεκριμένα συσχετίστηκε με τον υψηλότερο κίνδυνο για καρκίνο του μαστού (OR 2.25, 95% CI 1.45-3.49,p=0.0003). Παρομοίως, τα άτομα με τουλάχιστον ένα rs4645981 Τ αλληλόμορφο ήταν σε σημαντικά αυξημένο κίνδυνο να αναπτύξουν καρκίνο του μαστού συγκρινόμενα με εκείνα που έφεραν το CC γονότυπο (OR 2.75, 95% CI 1.99-3.78, p<0.0001) και ο κίνδυνος του καρκίνου του μαστού αυξανόταν όσο αυξανόταν ο αριθμός των rs4645981 Τ αλληλόμορφων (OR 2.66, 95% CI 1.91-3.69,